Until the discovery of insulin in the twentieth century, diabetes mellitus was a mortal disease with an unclear origin and physiology. Despite the appearance of the concept in an Egyptian papyrus dated c.1550 BC, and the documentation of its study by ancient Chinese, the term "diabetes" was only coined by the Greek Aretaeus in the second century AD. In Europe, the study of diabetes was largely ignored until the seventeenth century, when the characteristic sweet flavor of diabetic urine was first described. However, the link between diabetes and the pancreas was not discovered until 1889 by Minkowski and von Mering, long after the first description of the pancreatic islets by Paul Langerhans in 1869. One of the most significant milestones in the field was the discovery of insulin by Banting and collaborators in 1922, which led to the therapeutic development of insulin administration as a life-saving intervention for type 1 diabetic patients. On the other hand, the isolation of islets was first reported by Bensley in 1911, a critical technical achievement that paved the way for clinical islet transplantation. Here we discuss the history of islet isolation, since the firsts studies of diabetes by ancient civilizations to the birth and parallel evolution of islet isolation and transplantation.

Pancreatic islet transplantation is a promising therapy for Type I Diabetes. For many years the method used worldwide for islet purification in both rodent and human islet isolation has been Ficoll-based density gradients, such as Histopaque. However, it is difficult to purify islets in laboratories with staff limitations when large scale isolations are required. We hypothesized that filtration could be a more simple and fast alternative to obtain good quality islets. Four separate islet isolations were performed per method, comparing filtration and Histopaque purification with handpicking as the gold standard method for islet purity. Different parameters of quality were assessed: yield in number of islets per pancreas, purity by dithizone staining, viability by Fluorescein Diacetate/ Propidium Iodide vital staining and in vitro functionality assessed by Glucose Stimulated Insulin Secretion. Time efficiency and cost were also analyzed. The overall quality of the islets obtained both by Histopaque and filtration was good. Filtration saved almost 90 % of the time consumed by Histopaque purification, and was also cheaper. However, one-third of the islets were lost. Since human and rodent islets share similar size but different density, filtration appears as a purification method with potential interest in translation to clinic.

The aim of any pancreatic islet isolation is obtaining pure, viable and functional pancreatic islets, either for in vitro or in vivo purposes. The islets of Langerhans are complex microorgans with the important role of regulating glucose homeostasis. Imbalances in glucose homeostasis lead to diabetes, which is defined by the American Diabetes Association as a "group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both" (American Diabetes Association 2011). Currently, the rising demand of human islets is provoking a shortage of this tissue, limiting research and clinical practice on this field. In this scenario, it is essential to investigate and improve islet isolation procedures in animal models, while keeping in mind the anatomical and functional differences between species. This chapter discusses the main aspects of mouse islet isolation research, highlighting the critical factors and shortcomings to take into account for the selection and/or optimization of a mouse islet isolation protocol.

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Introduction: Post transplant lymphoproliferative disorders (PTLD) are a heterogenous group of lymphoid proliferation occurring in the setting of solid organ or BM transplantation. In this review we will consider the incidence and clinical features of this group of patients in our center. Material and Methods: In this study, we present the clinical and pathologic features of PTLD cases after liver transplantation (LT). In the period of liver transplantation we had 3 pathology confi rmed cases of PTLD out of 430 liver transplant cases. Results: Among 430 liver transplantation 3 cases were diagnosed as PTLD. Two of the patients were child (both 6 year-old) and the other was adult (45 year-old). One of the children was presented with diarrhea after 6 months of transplant and PTLD (polymorphic type) was diagnosed on duodenal biopsy, she expired despite of reducing the immunosuppressive therapy and starting of chemotherapy. The other child was present with cervical lymphadenopathy one year after transplant. He was also expired. The reason of liver transplantation was biliary atresia in both of them. The last one was an HCV positive male patient who presented with a very small cervical lymphnode( 1 cm) 1 year after liver transplant. He was diagnosed as Hodgkin's-like type of PTLD, now after 3 years he is doing well. In all the three case EBV was positive in the involved tissue. Conclusion: In conclusion, PTLD is a life treating disorder in liver transplant patients. According to the present data (3/430) it seems that the incidence of this disorder is lower than other parts of the world.

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